An intensive program of key improvement of the current TRS breast cancer imager will increase the number of detectors, the dynamic range, and the number of parameters measured leading to increased accuracy, resolution, area of coverage, dynamic range and feature detection ability based upon both absorption and fluorescence studies of intrinsic and extrinsic contrast agents. These improvements will be evaluated one by one by computer simulation and anecdotal human subject studies. Increased imaging performance will be studied using perturbative diffusive optical tomography (DOT) and will be tested with single and multiple optical heterogeneities as a function of source detector pairs, projection angles, frequencies and signal to noise ratios. These improvements will also be tested with anecdotal DOT images of human breast tumor exploiting these instrumental and theoretical improvements in which coregistration with gadolinium enhanced MRI fluorodeoxy glucose PET and histopathology afford gold standards. Anecdotal clinical data will then be processed for a) image reconstruction, and b) fitting procedures in MRI designated voxels. The primary images and fits will be based upon evaluation with gadolinium enhanced MRI or and with histopathology respectively. Other features, especially tumor oxygenation as estimated from hemoglobin saturation will be compared, for imaging reconstruction, with PET and, for tumor diagnostic capability, with histopathology. A similar two tiered analysis will be made of light scattering in normal and hormonally activated breast. In this way the capability of DOT for image reconstruction and feature extraction will be evaluated with adequate studies to ensure validation of these novel approaches to breast cancer detection. Large scale tests are available under other support where a direct comparison with not only MRI but also digital mammography, ultrasound and PET will secure the validation studies.